Chemotherapy + Immunotherapy for Breast Cancer

Overseen By Adrienne Gropper Waks, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors, Immunosuppressants

Disqualifiers: Uncontrolled hypertension, Diabetes, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 14-15 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for hormone receptor-positive breast cancer by combining chemotherapy and immunotherapy. Chemotherapy uses drugs to kill cancer cells, while immunotherapy helps the immune system fight the cancer. Participants will receive either Nab-Paclitaxel (a chemotherapy drug) or Pembrolizumab (an immunotherapy drug) to evaluate the effectiveness of these treatments both individually and in combination. The trial seeks individuals with breast cancer that hasn't spread and who have not yet received chemotherapy or hormone treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should avoid using potent CYP3A4 inhibitors like ketoconazole and erythromycin during the study. Participants on bisphosphonates can continue their therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that nab-paclitaxel is well tolerated, with most side effects being mild or moderate, such as tingling in the hands and feet. Since its introduction for breast cancer in 2005, extensive experience has been gained with its use.

Research suggests that pembrolizumab is generally safe when combined with chemotherapy, though it can cause serious side effects, such as inflammation in parts of the body, which may require treatment.

This trial is in an early phase, so there is limited information on the safety of these two treatments when used together. The trial aims to provide more insight into the safety of this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nab-Paclitaxel and Pembrolizumab for breast cancer because it merges chemotherapy with immunotherapy, offering a novel approach. Nab-Paclitaxel is a chemotherapy drug that targets fast-dividing cancer cells, while Pembrolizumab is an immunotherapy agent that helps the immune system recognize and attack cancer cells. By combining these two, the treatment not only directly attacks the cancer but also boosts the body's natural defenses, potentially leading to more effective outcomes than standard chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that nab-paclitaxel effectively treats breast cancer at various stages. In this trial, one group of participants will receive nab-paclitaxel. Studies indicate that this treatment leads to a better overall response, meaning the cancer shrinks or disappears, and it takes longer for the cancer to grow or spread. Another group will receive pembrolizumab, which, when combined with chemotherapy, significantly extends patient survival compared to chemotherapy alone. It also enables some patients to undergo less invasive surgeries. Both treatments have shown promise in managing breast cancer, offering hope for hormone receptor-positive cases. ^{2 6 7 8 9}

Who Is on the Research Team?

Adrienne Gropper Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with hormone receptor-positive, HER2-negative operable breast cancer larger than 2 cm without distant metastasis. They must not have had prior treatments for this cancer and agree to use contraception. Participants need normal organ/marrow function, no active autoimmune diseases or infections, and can't be on systemic steroids/immunosuppressants.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

My breast cancer is hormone receptor-positive and HER2-negative.

My breast cancer is operable and my tumor is at least 2 cm big.

Exclusion Criteria

You have been diagnosed with Hepatitis B or Hepatitis C.

I have a history of lung inflammation not caused by an infection.

You are allergic to pembrolizumab or any of the ingredients in it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nab-Paclitaxel and Pembrolizumab. Nab-Paclitaxel is administered weekly and Pembrolizumab every 3 weeks for a total of 14-15 weeks.

14-15 weeks

Weekly visits for Nab-Paclitaxel, every 3 weeks for Pembrolizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in PD-L1 expression and overall response rate.

2 years

Long-term Follow-up

Participants are monitored for disease-free survival and other long-term outcomes.

3 years from randomization

What Are the Treatments Tested in This Trial?

Interventions

• Biopsy
• Nab-Paclitaxel
• Pembrolizumab

Trial Overview The study tests chemotherapy (Nab-Paclitaxel) combined with immunotherapy (Pembrolizumab) in treating hormone receptor-positive breast cancer. It includes preoperative treatment and requires participants to undergo three research biopsies during the therapy.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 3 Interventions

* 2 weeks Pembrolizumab Run in * Biopsy will be performed * Post mono therapy Nab-Paclitaxel administered weekly * Post mono therapy Pembrolizumab administered every 3 weeks * Agents administered for a total of 14 weeks

Group II: Nab-Paclitaxel Experimental Treatment 3 Interventions

* 2 weeks Nab-Paclitaxel Run in * Biopsy will be performed * Post mono therapy Nab-Paclitaxel administered weekly * Post mono therapy Pembrolizumab administered every 3 weeks * Agents administered for a total of 15 weeks

Nab-Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Abraxane for:

• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer

Approved in European Union as Abraxane for:

• Breast cancer
• Pancreatic cancer

Approved in Canada as Abraxane for:

• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Adrienne G. Waks

Lead Sponsor

Trials

4

Recruited

240+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

In a study involving 74 patients with metastatic melanoma, nab-Paclitaxel showed a response rate of 21.6% in chemotherapy-naive patients and 2.7% in previously treated patients, indicating better efficacy in those who had not undergone prior treatment.

The treatment was well tolerated, with 78% of previously treated patients and 49% of chemotherapy-naive patients able to complete therapy without dose reductions, suggesting a favorable safety profile compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Hersh, EM., O'Day, SJ., Ribas, A., et al.[2020]

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

In a study of 81 women with early-stage estrogen receptor-positive breast cancer, nab-Paclitaxel showed significant antitumor activity with a good response rate (RCB 0+I) of 24.7%, indicating its effectiveness as a neoadjuvant treatment despite a higher than expected poor response rate (RCB III) of 28.4%.

The treatment was associated with low rates of severe toxicity, with neutropenia being the most common side effect, and an exploratory analysis suggested that overexpression of the SPARC protein in tumors may predict a complete response, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. Martín, M., Chacón, JI., Antón, A., et al.[2021]

Nab-paclitaxel (Abraxane) is an effective treatment for metastatic breast cancer, showing a superior therapeutic index compared to conventional paclitaxel in a Phase III study with a standard dose of 260 mg/m² every three weeks.

In patients with poor prognostic factors, nab-paclitaxel demonstrated rapid and significant tumor responses, indicating it may be particularly beneficial for those with more severe disease, and lower doses (100 and 150 mg/m² weekly) also showed promising efficacy, suggesting potential for dose tailoring in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the role of nab-paclitaxel (Abraxane) in women with aggressive metastatic breast cancer. Ciruelos, E., Jackisch, C.[2015]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

In a study of women with metastatic breast cancer treated with nab-paclitaxel, 43% experienced a clinical benefit, with a median survival of 63.6 weeks, indicating its effectiveness as a treatment option.

Nab-paclitaxel was well tolerated, with no severe hypersensitivity reactions reported and mild sensory neuropathy being the most common side effect, suggesting a favorable safety profile compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Study of Efficacy and Safety of Albumin-Bound Paclitaxel in Metastatic Breast Cancer. Singh, RK., Pankaj, S., Kumar, S., et al.[2022]

ABI-007, a solvent-free albumin-bound paclitaxel, showed significantly higher response rates (33% vs. 19%) and longer time to tumor progression (23.0 weeks vs. 16.9 weeks) compared to standard paclitaxel in a phase III study with 454 patients.

ABI-007 had a lower incidence of severe neutropenia (9% vs. 22%) and did not require premedication, indicating a better safety profile, although it was associated with a higher rate of manageable sensory neuropathy (10% vs. 2%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. Gradishar, WJ., Tjulandin, S., Davidson, N., et al.[2023]

Citations

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A Real-World Efficacy of Nab-Paclitaxel Monotherapy in ... In conclusion, this real-world data shows that nab-paclitaxel is an effective treatment option in metastatic breast cancer. Nab-paclitaxel was well tolerated ...

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nab-Paclitaxel for the treatment of breast cancer Recent clinical data indicate that nab-paclitaxel is effective and safe across all stages of breast cancer. The results from trials in the ...

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Nab-Paclitaxel: A New Standard of Care in Neoadjuvant ... Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) was approved in 2005 for the treatment of metastatic breast cancer, primarily on the basis of a phase ...

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Five-Year Dosing, Efficacy Results for Nab-Paclitaxel in ... For OS, ixabepilone was inferior, while nab-paclitaxel trended toward inferior in the HR+ subset, although ixabepilone was quite superior for PFS, at 21 months ...

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Final Effectiveness and Safety Results of NABUCCO The results of the NABUCCO study confirm the clinical trial outcomes and the favorable safety profile of nab-P in patients with metastatic breast cancer in a ...

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Safety and effectiveness of nab-paclitaxel in young and ... Overall, Nab-paclitaxel was well tolerated, with most adverse drug reactions (ADRs) mild or moderate in severity. The most common ADRs were peripheral ...

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Efficacy and safety of nanoparticle-albumin-bound ... Nab-paclitaxel also showed significantly longer OS (HR 0.73, 95% CI 0.54–0.99, p = 0.04) than docetaxel. AEs and DDR were comparable between the ...